2-aminooxazolines as TAAR1 ligands

Abstract

The invention relates to compounds of formula I wherein X, Y, R 1 , R 2 , and n are as defined herein or to a pharmaceutically suitable acid addition salt thereof. The invention also relates to pharmaceutical compositions containing such compounds and methods for the treatment of diseases related to the biological function of the trace amine associated receptors, which diseases include depression, anxiety disorders, bipolar disorder, attention deficit hyperactivity disorder, stress-related disorders, psychotic disorders, schizophrenia, neurological diseases, Parkinson's disease, neurodegenerative disorders, Alzheimer's disease, epilepsy, migraine, substance abuse and metabolic disorders, eating disorders, diabetes, diabetic complications, obesity, dyslipidemia, disorders of energy consumption and assimilation, disorders and malfunction of body temperature homeostasis, disorders of sleep and circadian rhythm, and cardiovascular disorders.

The invention claimed is: 
     
       1. A compound which is selected from the group consisting of
 (S)-4-(2-fluoro-4-trifluoromethyl-phenyl)-4-methyl-4,5-dihydro-oxazol-2-ylamine, 
 (RS)- 4-(4-fluoro-2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine, 
 (RS)-4-(5-chloro-2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine, 
 (RS)-4-(4-chloro-2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine, 
 (RS)-4-(4,5-dichloro-2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine, 
 (+)-(S)-4-(4-chloro-2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine, 
 (+)-(S)-4-(4,5-dichloro-2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine, 
 (−)-(R)-4-(4,5-dichloro-2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine, 
 (+)-(S)-4-(4-fluoro-2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine, 
 (RS)-4-(5-fluoro-2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine, 
 (RS)-4-(5-fluoro-2-methyl-phenyl)-4,5-dihydro-oxazol-2-ylamine, 
 (+)-(S)-4-(5-fluoro-2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine, 
 (RS)-4-(4-chloro-3-methyl-phenyl)-4-methyl-4,5-dihydro-oxazol-2-ylamine, 
 (RS)-4-(5-chloro-2-methyl-phenyl)-4,5-dihydro-oxazol-2-ylamine, 
 (RS)-4-(4-chloro-2-fluoro-5-methyl-phenyl)-4-methyl-4,5-dihydro-oxazol-2-ylamine, 
 (S)-4-(4-chloro-3-methyl-phenyl)-4-methyl-4,5-dihydro-oxazol-2-ylamine, 
 (RS)-4-(4-bromo-2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine, 
 (S)-4-(4-chloro-2-fluoro-5-methyl-phenyl)-4-methyl-4,5-dihydro-oxazol-2-ylamine, 
 (+)-(S)-4-(5-chloro-2-methyl-phenyl)-4,5-dihydro-oxazol-2-ylamine, 
 (RS)-4-(4-fluoro-2-methyl-phenyl)-4,5-dihydro-oxazol-2-ylamine, 
 (+)-(S)-4-(4-bromo-2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine, 
 (+)-(S)-4-(5-chloro-2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine, 
 (RS)-4-(4-chloro-2-ethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine, 
 (+)-(S)-4-(4-fluoro-2-methyl-phenyl)-4,5-dihydro-oxazol-2-ylamine, 
 (RS)-4-(3-chloro-4-methyl-phenyl)-4,5-dihydro-oxazol-2-ylamine, 
 (RS)-4-(4-chloro-2-cyclopropyl-phenyl)-4,5-dihydro-oxazol-2-ylamine, 
 (S)-4-(4-chloro-2-ethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine, 
 (RS)-4-(3-fluoro-2-methyl-phenyl)-4,5-dihydro-oxazol-2-ylamine, 
 (S)-4-(4-chloro-2-cyclopropyl-phenyl)-4,5-dihydro-oxazol-2-ylamine, 
 (RS)-4-(3-fluoro-2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine, and 
 (S)-4-(3-chloro-4-methyl-phenyl)-4,5-dihydro-oxazol-2-ylamine. 
 
     
     
       2. A pharmaceutical composition comprising a compound or a pharmaceutically suitable acid addition salt thereof and a pharmaceutically acceptable carrier, wherein the compound is selected from the group consisting of
 (S)-4-(2-fluoro-4-trifluoromethyl-phenyl)-4-methyl-4,5-dihydro-oxazol-2-ylamine, 
 (RS)- 4-(4-fluoro-2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine, 
 (RS)-4-(5-chloro-2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine, 
 (RS)-4-(4-chloro-2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine, 
 (RS)-4-(4,5-dichloro-2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine, 
 (+)-(S)-4-(4-chloro-2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine, 
 (+)-(S)-4-(4,5-dichloro-2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine, 
 (−)-(R)-4-(4,5-dichloro-2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine, 
 (+)-(S)-4-(4-fluoro-2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine, 
 (RS)-4-(5-fluoro-2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine, 
 (RS)-4-(5-fluoro-2-methyl-phenyl)-4,5-dihydro-oxazol-2-ylamine, 
 (+)-(S)-4-(5-fluoro-2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine, 
 (RS)-4-(4-chloro-3-methyl-phenyl)-4-methyl-4,5-dihydro-oxazol-2-ylamine, 
 (RS)-4-(5-chloro-2-methyl-phenyl)-4,5-dihydro-oxazol-2-ylamine, 
 (RS)-4-(4-chloro-2-fluoro-5-methyl-phenyl)-4-methyl-4,5-dihydro-oxazol-2-ylamine, 
 (S)-4-(4-chloro-3-methyl-phenyl)-4-methyl-4,5-dihydro-oxazol-2-ylamine, 
 (RS)-4-(4-bromo-2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine, 
 (S)-4-(4-chloro-2-fluoro-5-methyl-phenyl)-4-methyl-4,5-dihydro-oxazol-2-ylamine, 
 (+)-(S)-4-(5-chloro-2-methyl-phenyl)-4,5-dihydro-oxazol-2-ylamine, 
 (RS)-4-(4-fluoro-2-methyl-phenyl)-4,5-dihydro-oxazol-2-ylamine, 
 (+)-(S)-4-(4-bromo-2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine, 
 (+)-(S)-4-(5-chloro-2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine, 
 (RS)-4-(4-chloro-2-ethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine, 
 (+)-(S)-4-(4-fluoro-2-methyl-phenyl)-4,5-dihydro-oxazol-2-ylamine, 
 (RS)-4-(3-chloro-4-methyl-phenyl)-4,5-dihydro-oxazol-2-ylamine, 
 (RS)-4-(4-chloro-2-cyclopropyl-phenyl)-4,5-dihydro-oxazol-2-ylamine, 
 (S)-4-(4-chloro-2-ethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine, 
 (RS)-4-(3-fluoro-2-methyl-phenyl)-4,5-dihydro-oxazol-2-ylamine, 
 (S)-4-(4-chloro-2-cyclopropyl-phenyl)-4,5-dihydro-oxazol-2-ylamine, 
 (RS)-4-(3-fluoro-2-trifluoromethyl-phenyl)-4,5-dihydro-oxazol-2-ylamine, and 
 (S)-4-(3-chloro-4-methyl-phenyl)-4,5-dihydro-oxazol-2-ylamine 
 
       or a pharmaceutically suitable acid addition salt thereof.